Human embryo fibroblasts T-38 and HLM15 in culture undergo a period of rapid proliferation which is followed by a decline in the rate of cell division and the eventual degeneration of the culture. Hayflick and Moorhead (1961) have suggested that the basis for this phenomenon is genetically intrinsic to the cell and may represent aging at the cellular level. The cell surface appears to have the function of a sensory organelle for a single cell, and much recent evidence indicates the cell may use this function to its advantage in the regulation of cell division and cell development according to signals dictated by the cellular environment. Whether gene products expressed at the cell surface differentiate with age and whether they play a role in the senescent behavior of cells aging in culture is presently unknown and is the subject of this proposal. Hence, specific objectives of this research include (1) characterization of cycle-dependent alterations in surface topography of early, middle and late passage human embryo fibroblasts and their virus-transformed derivatives, utilizing techniques of scanning electron microscopy; (2) an analysis of binding patterns of plant lectins (specifically Concanavalin A and wheat germ agglutinin) on exterior surfaces of cycling phase II and senescent phase III cells by techniques of flow microfluorometry and electron microscopy and (3) investigation of whether age- or experimentally-induced alterations in cell surface components may be associated with receptivity and/or activity of adenylate cyclase in the cell membrane. BIBLIOGRAPHIC REFERENCES: Kelley, R.O. Ultrastructural identification of extracellular matrix and cell surface components with ruthenium red and Concanavalin A during limb morphogenesis in man. J. Embryol. Exp. Morph. 34: 1-18, 1975. Kelley, R.O., and G.C. Palmer Mediation of mesenchymal cell development during human limb morphogenesis through glycosaminoglycan-adenylate cyclase interaction at the cell surface. In: Embryogenesis in Mammals, pp. 275-290, Associated Scientific Publishers, London, 1976.